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Pediatric Pharm Exam 3 > Anxiety and Depression > Flashcards

Anxiety and Depression Flashcards

1
Q

Types of endogenous NTs (4)

A
  1. Serotonin (5-HT)
    * 14 different receptor subtypes
    * found in different parts of the body from brain to gut
  2. Norepinephrine (NE)
  3. Dopamine (DA)
  4. Gamma-aminobutyric acid (GABA)
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2
Q

Other functions of NTs (3)

A
  1. Platelet aggregation and function (5-HT)
  2. Vasoconstriction (DA)
  3. GI signaling (DA and 5-HT) found in GI tract & blood vessels
    * Many side effects will be occur because receptors are scattered throughout the body
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3
Q

Common psychiatric disorders where medications may be useful (11)

A
  1. Anxiety
  2. Attention-deficit anxiety disorder (ADHD)
  3. Autism
  4. Bedwetting
  5. Bipolar disorder
  6. Depression
  7. Eating disorders
  8. Obsessive-compulsive disorder (OCD)
  9. Psychosis
  10. Severe aggression
  11. Sleep disorders
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4
Q

Anxiety signs and symptoms (2)

A
  1. Fear or worry

2. Somatic symptoms (headache, stomach ache)

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5
Q

Common anxiety triggers (4)

A
  1. Social (family, friends, social phobia)
  2. Schoolwork
  3. Major world event or disasters
  4. Medical Procedures
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6
Q

Anxiety Treatments (3)

A
  1. Cognitive behavioral therapy
  2. Psychotherapy
  3. Drugs can used as adjunctive treatment
    - SSRIs
    - Benzodiazepines for acute episodes
    - Propranolol
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7
Q

Alprazolam (Xanax) Onset, Half Life, and Active Metabolite/Metabolism

A

Onset: 60 minutes

Half-Life: ~11 hours

Active Metabolite/Metabolism: Yes/Hepatic

*Remember there are active metabolites for Alprazolam and Diazepam so they will be in the system for much longer if you have hepatic impairment

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8
Q

Clonazepam (Klonopin) Onset, Half Life, and Active Metabolite/Metabolism

A

Onset: 20-40 minutes

Half-Life: 22-33 hours

Active Metabolite/Metabolism: No/hepatic

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9
Q

Diazepam (Valium) Onset, Half Life, and Active Metabolite/Metabolism

A

Onset: 10-20 minutes

Half-Life: Up to 48 hours

Active Metabolite/Metabolism: Yes/hepatic

*Remember there are active metabolites for Alprazolam and Diazepam so they will be in the system for much longer if you have hepatic impairment

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10
Q

Lorazepam (Ativan) Onset, Half Life, and Active Metabolite/Metabolism

A

Onset: 30-60 minutes

Half-Life: ~15 hours

Active Metabolite/Metabolism: No/hepatic

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11
Q

Benzodiazepine Agents, Mechanisms of Action, and Routes

A
  1. Alprazolam (Xanax)
  2. Clonazepam (Klonopin)
  3. Diazepam (Valium)
  4. Lorazepam (Ativan)

Mechanism of action: binds to GABA receptors halting neuronal stimulation

Routes: PO, IV for status epilepticus, IN for emergent use

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12
Q

Benzodiazepine ADEs (5)

A
  1. Respiratory depression
  2. Hypotension, bradycardia
  3. Delirium
  4. Paradoxical agitation
  5. Short term memory loss (can be a benefit)
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13
Q

Cautions/BBWs with Benzodiazepines (2)

A
  1. BBW with opioid use; can cause greater risk of hypotension and respiratory depression
  2. Caution with oral liquid solutions and propylene glycol
    * Caution in use with neonates
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14
Q

Benzodiazepine Metabolism (2)

A
  1. Most undergo hepatic metabolism

2. Drug-drug interactions with CYP450 enzymes; CYP3A4 in particular

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15
Q

Benzodiazepine Elimination (2)

A
  1. All are renally excreted

2. > risk of over sedation and/or prolonged sedation if active metabolites present & renal impairment

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16
Q

Benzodiazepine Recommendations

A

Generally recommended for short-time use; prolonged use causes increased tolerance (more medication needed to do the same effect)
*Withdrawal associated with seizures

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17
Q

Benzodiazepine Place in Therapy (3)

A
  1. Short term use (i.e. PRN)
  2. Not maintenance therapy
  3. Agent of choice depends on duration of use (i.e. short duration versus longer acting)
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18
Q

Benzodiazepine Withdrawal

A

Acute withdrawal following prolonged use is associated with seizures; General taper schedule is 20% every other day until unmeasurable dose or < 0.05 mg/kg per dose

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19
Q

Other Benzodiazepine Uses

A
  1. Nausea/vomiting
  2. Sedation
  3. Acute alcohol withdrawal
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20
Q

Major Depressive Disorder Medications (3)

A
  1. SSRIs/SNRIs
  2. TCAs
  3. MAOIs
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21
Q

Receptor Selectivity: Which drugs are highly selective to SE? (6)

A
  1. Citalopram –> 1.1 selectivity
  2. Escitalopram –> 1.4
  3. Sertaline –> 0.3
  4. Fluvoxamine –> 2.2
  5. Fluoxetine –> 0.8
  6. Duloxetine –> 1.6 (but this drug is more selective to DA)
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22
Q

Receptor Selectivity: Which drugs are highly selective to NE? (3)

A
  1. Desipiramine –> 0.8
  2. Atomaxetine –> 3.5
  3. Nortripytline –> 4.4
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23
Q

Receptor Selectivity: Which drugs are highly selective to DA? (3)

A
  1. Buproprion –> 526 (more than SE and NE)
  2. Duloxetine –> 0
  3. Sertaline –> 25
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24
Q

SSRI vs. SNRI General Considerations (4)

A
  1. Selectivity
  2. Side effect profile
  3. Cost
    * Insurance companies dictate a lot about the drug to choose based on cost
  4. Patient tolerability/effect
    * 20 – 50% will not respond (adult literature)
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25
Q

SSRI Mechanism of Action (4)

A
  1. Binds to SRR preventing serotonin from being taken back into the pre-synaptic cell
  2. Increased serotonin in synaptic cleft
  3. Increased serotonin binding to post-synaptic receptors
  4. Prevent reuptake of 5HT from pre-synaptic cell
    * Blocking the receptor to increase 5HT levels at the synaptic cleft so that more 5HT can bind to post-synaptic cell and increase signaling
26
Q

SSRI Onset of Action (3 including tapering)

A
  1. Actual beneficial effect can be delayed
    * Effect typically takes 2 – 4 weeks after starting treatment
    * Some patients report “feeling better” within a few days
  2. Initially starting therapy can increase symptoms
    * Monitor for increase in harmful or suicidal ideation
    * BBW: Increased suicidal ideation, especially in adolescents
  3. Acutely stopping can lead to abrupt onset of anxiety and depression
    * Taper off medications is recommended with drugs with shorter half-life (i.e. paroxtine) → especially if they have been on it for a week or more
    * Longer taper for the longer amount of time they have taken the drug
27
Q

Citalopram (Celexa) PK (substrates and half life)

A

SSRI

  1. CYP3A4, 2C19, 2D6
  2. Half life: 35 hours
28
Q

Escitalopram (Lexapro) PK (substrates and half life)

Approved >

A

SSRI

  1. CYP3A4, 2C19
  2. Half life: ~30 hours

Approved > 12 years

29
Q

Fluoxetine (Prozac) PK (substrates, half life and active metabolite)

Approved >

A

SSRI

  1. CYP2CP and 2D6
  2. Half life: 4-6 days
  3. Active metabolite: half life of 7-9 ayes

Approved over 8 years

30
Q

Fluvoxamine PK (substrates and half life)

A

SSRI

  1. CYP1A2 and 2D6
  2. Half life: 16 hours
    * only one approved for pediatric OCD
31
Q

Paroxetine (Paxil) PK (substrates and half life)

A

SSRI

  1. CYP2D6
  2. Half life: 24 hours
32
Q

Sertaline (Zoloft) PK (substrate, half life and active metabolite)

Approved >

A

SSRI

  1. CYP3A4, 2C19, 2C9, 2D6
  2. Half life: 26 hours
  3. Active metabolite: half life of 70-80 hours

Approved > 6 years

33
Q

Citalopram and Escitalopram ADEs (2)

A
  1. GI distress

2. Weight gain

34
Q

Fluoxetine and Sertaline ADE

A

GI distress

35
Q

Paroxetine ADEs (3)

A

SSRI

  1. Sedation
  2. GI distress
  3. Weight gain
36
Q

Duloxetine and Venlafaxine ADEs (3)

A

SNRI

  1. GI distress
  2. Conduct abnormalities
  3. Sedation
37
Q

Duloxetine (Cymbalta) available dosage form and PK parameters

A

SNRI

Available dosage form: delayed release capsules

PK parameters:

  1. Half life - ~12 hours
  2. CYP1A2 and CYP2D6 substrate
38
Q

Venlafaxine (Effexor) available dosage form and PK parameters

A

SNRI

  1. Available dosage forms: tablet capsule
  2. Half life - depends on dosage form
  3. CYP3A4 substrate (does not effect other enzymes)
39
Q

SSRIs/SNRI BBW

A

Increased risk of suicidal ideation

40
Q

Duloxetine ADEs (6)

A

SNRI

  1. Drowsiness or insomnia
  2. Nausea
  3. Abdominal pain
  4. Constipation
  5. Weight gain or loss
  6. Headache
41
Q

Venlafaxine ADEs (5)

A

SNRI

  1. Sedation
  2. Increased BP
  3. GI distress
  4. Weight gain or loss
  5. Abnormal dreams
42
Q

Desvenlafaxine ADEs (4)

A

SNRI

  1. Increased BP
  2. N/V/D
  3. Insomnia
  4. Decreased appetite
43
Q

SSRI/SNRI General Precautions (6)

A
  1. May take several weeks to see full effect
  2. Titrate slowly (every 2-3 weeks)
    * If one medication does not work when titrated to maximum dose, switch to another medication
  3. Use associated with increased risk of suicide
    * Especially in adolescent age group

CAUTION with…

  1. Heart rhythm abnormalities
  2. Serotonin syndrome
  3. Platelet dysfunction
44
Q

Serotonin Syndrome (3)

A
  1. Life-threatening hyperthermia, seizure medical emergency
    * Or it can cause milder symptoms of tremor, altered mental status, etc.
  2. Can be dose-specific or not
  3. Increases when used in combination with multiple medications
45
Q

Serotonin syndrome proposed mechanism

A

Too much 5HT in synaptic cleft causes over-excitation of neuron

  • Hyperstimulation leading to the side effects
  • Main concern is hyperthermia
46
Q

Drugs associated with 5HT Syndrome (13)

A

MUST KNOW FOR EXAM

  1. SSRI/SNRIs
  2. MAOIs
  3. TCAs
  4. Lithium
  5. Fentanyl
  6. Ondansetron
  7. granisetran
  8. sumitriptan
  9. Metoclopramide
  10. Linezolid
  11. Tryptophan
  12. Tramadol
  13. Valproatic acid
47
Q

Tricyclic Antidepressants Mechanism of Action

A

Inhibits the re-uptake of 5-HT and NE increasing synaptic concentrations

48
Q

TCA Agents Available for MDD (4)

A
  1. Doxepin
  2. Amitriptyline
  3. Imipramine
  4. Nortriptyline
49
Q

TCA Pearls (4)

A
  1. May take several weeks to reach full affect
    * Titrate slowly
  2. Due to side effects not routinely used first line especially in pediatrics
  3. CAUTION with heart rhythm abnormalities
  4. VERY dangerous in overdoses
50
Q

Amitriptyline ADEs (6)

A

TCA

  1. Anti-cholinergic effects ++++
  2. Sedation ++++
  3. Decreased BP +++
  4. Abnormal conduct+++
  5. GI distress +
  6. Weight gain ++++
51
Q

Doxepin ADEs (5)

A

TCA

  1. Anticholinergic effects +++
  2. Sedation ++++
  3. Decreased BP ++
  4. Abnormal conduct ++
  5. Weight gain ++++
52
Q

Imipramine ADEs (6)

A

TCA

  1. Anticholinergic effects +++
  2. Sedation +++
  3. Decreased BP ++++
  4. Abnormal conduct +++
  5. GI distress +
  6. Weight gain ++++
53
Q

Nortriptyline ADEs (5)

A

TCA

  1. Anticholinergic effects ++
  2. Sedation ++
  3. Decreased BP +
  4. Abnormal conduct ++
  5. Weight gain +
54
Q

Dopamine Reuptake Blockers MOA (4)

A
  1. Structurally different than all other antidepressants
  2. MOA not fully understood
  3. Dopaminergic and noradrenergic activity
  4. Weak inhibitor of dopamine and norepinephrine
    * No inhibition of serotonin
    * Won’t see anticholinergic/BP side effects
55
Q

DA Reuptake Blocker Agent

A

Buproprion (Wellbutrin)

56
Q

Buproprion ADEs (2)

A
  1. Abnormal Conduct

2. GI distress

57
Q

Buproprion Place in therapy (1) and useful for (3)

A

Place in therapy:
1, Depression refractory to SSRIs/SNRIs

Useful for

  1. Older patients with ADD/ADHD
  2. Older patients with SAD
  3. Smoking cessation
58
Q

Noradrenergic Antagonists MOA

A
  1. Tetracyclic antidepressant
  2. Increases release of norepinephrine and serotonin
    * Does not inhibit reuptake
59
Q

Noradrenergic Antagonist Agent

A

Mirtazapine (Remeron)

60
Q

Mirtazapine (Remeron) ADEs (5)

A
  1. Anticholinergic effects +
  2. Sedation +++
  3. Decreased BP +
  4. Conduct abnormal +
  5. Weight gain +++
61
Q

Mirtazapine (Remeron) Place in therapy

A

Depression refractory to SSRIs/SNRIs

62
Q

Mirtazapine (Remeron) Contraindications

A

Contraindicated with MAOIs or linezolid

*Requires 14 day ‘wash out’

Pediatric Pharm Exam 3 (11 decks)

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